Aggregation/Crystallization-Induced Emission in Naphthyridine-Based Carbazolyl-Modified Donor-Acceptor Boron Dyes Tunable by Fluorine Atoms.

Four donor-acceptor boron difluoride complexes based on the carbazole electron donor and the [1,3,5,2]oxadiazaborinino[3,4-a][1,8]naphthyridine acceptor were designed, synthesized, and systematically spectroscopically investigated in solutions, in dye-doped polymer films, and in the solid states. The dyes exhibit an intense blue to red solid-state emission with photoluminescence quantum yields of up to 59 % in pure dye samples and 86 % in poly(methyl methacrylate) films. All boron complexes show aggregation-induced emission and reversible mechanofluorochromism. The optical properties of these dyes and their solid state luminescence can be tuned by substitution pattern, i. e., the substituents at the naphthyridine unit. Exchange of CH3- for CF3-groups does not only increase the intramolecular charge transfer character, but also provides a crystallization-induced emission enhancement.

Carbazole-modified thiazolo[3,2-c][1,3,5,2]oxadiazaborinines exhibiting aggregation-induced emission and mechanofluorochromism.

Two highly emissive carbazole-containing thiazole-fused oxadiazaborinines were designed and synthesized. These N,O-chelated organoboron dyes displayed large Stokes shifts and remarkable solvatofluorochromism in solutions, as well as good thermal stability and comparatively high photoluminescence quantum yields (up to 34%) in the solid state. The presence of a carbazole donor unit, linked with the oxadiazaborinine acceptor via a phenyl linker, restricted intramolecular rotation, leading to enhanced aggregation-induced emission properties of the compounds: in THF/water mixtures with a large water percentage, they demonstrated the formation of emissive nanoaggregates with an average size of 79 and 89 nm for complexes 2 and 3, respectively. The introduction of bulky tert-butyl groups attached to the carbazole moiety induced significant mechanofluorochromic properties of the compounds.

Covalent inhibition of NSD1 histone methyltransferase.

The nuclear receptor-binding SET domain (NSD) family of histone methyltransferases is associated with various malignancies, including aggressive acute leukemia with NUP98-NSD1 translocation. While NSD proteins represent attractive drug targets, their catalytic SET domains exist in autoinhibited conformation, presenting notable challenges for inhibitor development. Here, we employed a fragment-based screening strategy followed by chemical optimization, which resulted in the development of the first-in-class irreversible small-molecule inhibitors of the nuclear receptor-binding SET domain protein 1 (NSD1) SET domain. The crystal structure of NSD1 in complex with covalently bound ligand reveals a conformational change in the autoinhibitory loop of the SET domain and formation of a channel-like pocket suitable for targeting with small molecules. Our covalent lead-compound BT5-demonstrates on-target activity in NUP98-NSD1 leukemia cells, including inhibition of histone H3 lysine 36 dimethylation and downregulation of target genes, and impaired colony formation in an NUP98-NSD1 patient sample. This study will facilitate the development of the next generation of potent and selective inhibitors of the NSD histone methyltransferases.

Synthesis of Highly Oxygenated Bicyclic Carbasugars. Remarkable Difference in the Reactivity of the d-gluco and d-xylo- Derived Trienes.

2,3,4-Tri-O-benzyl-D-xylopyranose was used as a starting material in the preparation of the corresponding triene, which underwent smooth cyclization to a polyhydroxylated hydrindane, as a single diastereoisomer. The analogous triene prepared from D-glucose did not undergo any cyclization even under high pressure.

Organolithium-Mediated Postfunctionalization of Thiazolo[3,2-c][1,3,5,2]oxadiazaborinine Fluorescent Dyes.

An effective method for transition-metal-free postfunctionalization of thiazolo[3,2-c][1,3,5,2]oxadiazaborinine dyes via direct lithiation of the 1,3-thiazole ring was developed. The reaction allows valuable regioselective C-H modification of these N,O-chelated organoboron chromophores incorporating different groups, including C-, Hal-, Si-, S-, Se-, and Sn-substituents. As a result, a library of novel fluorescent 1,3-thiazole-based organoboron complexes has been synthesized and characterized. The influence of the donor/acceptor strength of the substituent E on the photophysical properties has been established. The compound with a bulky lipophilic substituent (SnBu3) exhibits a relatively high solid-state photoluminescence quantum yield of 44%.

Stereocontrolled Debenzylative Cycloetherification Reaction as a Route to Enantiopure C-Furanosides with Amino Substituents in the Side Chain.

A highly efficient methodology of the preparation of synthetically important tetrahydrofuran derivatives with an amino substituent in the side chain is reported. This process is based on the stereocontrolled debenzylative cycloetherification (DBCE) reaction applied for chirons from the d-gluco- and d-manno-series and provides derivatives with new stereogenic centers. The influence of the electron-withdrawing group (EWG), present in the acyclic substrates with the mesyl leaving group, on the reactivity in the DBCE reaction was investigated both "in the flask" and by density functional theory (DFT) calculations. It was demonstrated that tetrahydrofuran derivatives with the benzoxime group (EWG = CHNOBn) are very good candidates for the subsequent highly stereoselective Grignard reaction.

Synthesis of Cyclotriveratrylene-Sucrose-Based Capsules.

Cyclotriveratrylene (CTV) is a C3-symmetrical macrocycle, which can be used as a chiral building block in the construction of supramolecular containers. Coupling of the CTV unit with a sucrose molecule gave enantiopure water-soluble (after deprotection) containers. The absolute configuration of the synthesized capsules was determined by NMR and ECD spectroscopies and DFT calculations.

Application of the Suzuki-Miyaura Reaction for the Postfunctionalization of the Benzo[4,5]thiazolo[3,2- c][1,3,5,2]oxadiazaborinine Core: An Approach toward Fluorescent Dyes.

A fluorescent dye based on the 8-brominated benzo[4,5]thiazolo[3,2- c][1,3,5,2]oxadiazaborinine core was synthesized from benzo[ d]thiazol-2-amine. The new boron complex can be effectively modified by a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with (het)arylboronic acids. This reaction allows a valuable regioselective postfunctionalization of 1,3,5,2-oxadiazaborinine chromophores with different aromatic substituents. The solutions of obtained target complexes in organic solvents demonstrate high fluorescence quantum yields. The compound with a 4-cyanophenyl group at benzothiazole unit (Ar = 4-C6H4CN) exhibits a comparatively high fluorescence quantum yield of 0.31 in the solid state.

Benzo[4,5]thiazolo[3,2- c][1,3,5,2]oxadiazaborinines: Synthesis, Structural, and Photophysical Properties.

A family of highly emissive benzo[4,5]thiazolo[3,2- c][1,3,5,2]oxadiazaborinines, conjugated with the donor 4-dimethylaminophenyl group, was designed and synthesized. Their photophysical, both in solution and in the solid state, and structural properties were investigated. The influence of donor and acceptor substituents (R) in the benzothiazole unit on photophysical properties of complexes was found out. The tetrafluorobenzothiazole analogue exhibits nonbonded nuclear spin-spin coupling between fluorines from the BF2 group and α-fluorine atom at the benzene ring. Additionally, this boron complex demonstrates a comparatively high solid-state fluorescence quantum yield (Φ = 0.34).

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms".

An efficient methodology for the selective substitution of both terminal positions (C6 and C6') in 1',2,3,3',4,4'-hexa-O-benzylsucrose with different unsaturated monosaccharide units is presented. Such a highly functionalized intermediate was cyclized under RCM conditions to afford a macrocyclic derivative containing a 31-membered ring in 26% yield.

N,O π-Conjugated 4-Substituted 1,3-Thiazole BF2 Complexes: Synthesis and Photophysical Properties.

A series of 1,3-thiazole-based organoboron complexes has been designed and synthesized by acylation of 2-amino 4-subsituted 1,3-thiazoles with (4-dimethylamino)benzoyl chloride and the subsequent BF2 complexation reaction. The influence of substituents in position 4 of the thiazole ring on photophysical properties of the complexes has been investigated. Synthesized thiazolo[3,2-c][1,3,5,2]oxadiazaborinines mainly showed intensive fluorescence in solutions. Complex with a 4,5-unsubstituted thiazole unit demonstrated an aggregation induced emission (AIE) effect and a very high fluorescent quantum yield (94%) in the solid state because of the inhibition of π-π/π-n interactions in the molecular packing.

An efficient synthesis of a C12-higher sugar aminoalditol.

The C12-aminoalditol H2NCH2-(CHOBn)10-CH2OH was prepared from two simple monosaccharide building blocks. The synthesis was realized by a regioselective introduction of the azide group and subsequent protection-deprotection transformations. The chemical reactivity of the aminoalditol was tested in the reductive amination reaction with a selectively protected sucrose monoaldehyde.

Nitrogen-containing macrocycles having a carbohydrate scaffold.

Nitrogen-containing macrocyclic compounds (amines, amides, and N-heterocyclic derivatives) are important targets in supramolecular chemistry. This chapter discusses the importance of aza-macrocycles in general and, in particular, those receptors containing sugar unit(s). The combination of a carbohydrate scaffold bearing nitrogen-containing functional groups in macrocyclic molecules opens a convenient route to chiral receptors having potentially useful properties. The carbohydrate-based macrocycles discussed are classified into several general groups: (1) aza-crown ethers containing a carbohydrate subunit, (2) cyclic homooligomers from amino sugars, (3) sugar-based cryptands, (4) cyclic peptides containing amino sugar units (including C2- and C3-symmetrical macrocyclic glycopeptides), (5) nitrogen- containing glycophanes, and (6) 1,2,3-triazoles containing synthetic cyclodextrin analogues. The general strategies employed, as well as specific ones leading to such complex derivatives, are surveyed. Applications of such carbohydrate receptors, pointing to their importance as hosts in supramolecular chemistry, are discussed.

An efficient synthesis of novel sucrose-containing dilactams.

ABSTRACT: An efficient and convenient approach to sucrose-containing dilactams has been developed. The method, based on reaction of regioisomeric 6,6'-di-O-[(aminomethyl)-phenyl]-1',2,3,3',4,4'-hexa-O-methylsucrose with isophtaloyl or 2,6-pyridinedicarbonyl dichlorides, provided the 1:1-macrocycles in good yields. GRAPHICAL ABSTRACT: .

Short synthesis of diamide-linked sucrose macrocycles.

A convenient route to macrocyclic diamide-linked macrocyclic derivatives with a sucrose scaffold is presented. Reaction of sucrose based amines (o- and m-) with acid dichlorides afforded the monomeric macrocycles in excellent yields, while reaction of the p-amines also provided dimeric products.